Browse
Submit Data
Databases
API
Help

Dataset Information

22 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The Therapeutic Potential of Celastrol in Central Nervous System Disorders: Highlights from In Vitro and In Vivo Approaches.

ABSTRACT: Celastrol, the most abundant compound derived from the root of Tripterygium wilfordii, largely used in traditional Chinese medicine, has shown preclinical and clinical efficacy for a broad range of disorders, acting via numerous mechanisms, including the induction of the expression of several neuroprotective factors, the inhibition of cellular apoptosis, and the decrease of reactive oxygen species (ROS). Given the crucial implication of these pathways in the pathogenesis of Central Nervous System disorders, both in vitro and in vivo studies have focused their attention on the possible use of this compound in these diseases. However, although most of the available studies have reported significant neuroprotective effects of celastrol in cellular and animal models of these pathological conditions, some of these data could not be replicated. This review aims to discuss current in vitro and in vivo lines of evidence on the therapeutic potential of celastrol in neurodegenerative diseases, including Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, and cadmium-induced neurodegeneration, as well as in psychiatric disorders, such as psychosis and depression. In vitro and in vivo studies focused on celastrol effects in cerebral ischemia, ischemic stroke, traumatic brain injury, and epilepsy are also described.

SUBMITTER: Schiavone S

PROVIDER: S-EPMC8347599 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Allosteric Modulation of Ionotropic Glutamate Receptors: An Outlook on New Therapeutic Approaches To Treat Central Nervous System Disorders.

Project description:The allosteric targeting of ionotropic glutamate receptors (iGluRs) is a valuable approach for treating various central nervous system (CNS) disorders. In this frame, this Innovations provides a summary of the state-of-the art in the development of allosteric modulators for iGluRs and offers an outlook regarding innovative strategies for treating neurological diseases.

| S-EPMC6421537 | biostudies-literature

Passive Immunotherapies for Central Nervous System Disorders: Current Delivery Challenges and New Approaches.

Project description:Passive immunotherapy, i.e., the administration of exogenous antibodies that recognize a specific target antigen, has gained significant momentum as a potential treatment strategy for several central nervous system (CNS) disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and brain cancer, among others. Advances in antibody engineering to create therapeutic antibody fragments or antibody conjugates have introduced new strategies that may also be applied to treat CNS disorders. However, drug delivery to the CNS for antibodies and other macromolecules has thus far proven challenging, due in large part to the blood-brain barrier and blood-cerebrospinal fluid barriers that greatly restrict transport of peripherally administered molecules from the systemic circulation into the CNS. Here, we summarize the various passive immunotherapy approaches under study for the treatment of CNS disorders, with a primary focus on disease-specific and target site-specific challenges to drug delivery and new, cutting edge methods.

| S-EPMC7234797 | biostudies-literature

The therapeutic potential of insulin-like growth factor-1 in central nervous system disorders.

Project description:Central nervous system (CNS) development is a finely tuned process that relies on multiple factors and intricate pathways to ensure proper neuronal differentiation, maturation, and connectivity. Disruption of this process can cause significant impairments in CNS functioning and lead to debilitating disorders that impact motor and language skills, behavior, and cognitive functioning. Recent studies focused on understanding the underlying cellular mechanisms of neurodevelopmental disorders have identified a crucial role for insulin-like growth factor-1 (IGF-1) in normal CNS development. Work in model systems has demonstrated rescue of pathophysiological and behavioral abnormalities when IGF-1 is administered, and several clinical studies have shown promise of efficacy in disorders of the CNS, including autism spectrum disorder (ASD). In this review, we explore the molecular pathways and downstream effects of IGF-1 and summarize the results of completed and ongoing pre-clinical and clinical trials using IGF-1 as a pharmacologic intervention in various CNS disorders. This aim of this review is to provide evidence for the potential of IGF-1 as a treatment for neurodevelopmental disorders and ASD.

| S-EPMC4790729 | biostudies-literature

Targeting protein kinases in central nervous system disorders.

Project description:Protein kinases are a growing drug target class in disorders in peripheral tissues, but the development of kinase-targeted therapies for central nervous system (CNS) diseases remains a challenge, largely owing to issues associated specifically with CNS drug discovery. However, several candidate therapeutics that target CNS protein kinases are now in various stages of preclinical and clinical development. We review candidate compounds and discuss selected CNS protein kinases that are emerging as important therapeutic targets. In addition, we analyse trends in small-molecule properties that correlate with key challenges in CNS drug discovery, such as blood-brain barrier penetrance and cytochrome P450-mediated metabolism, and discuss the potential of future approaches that will integrate molecular-fragment expansion with pharmacoinformatics to address these challenges.

| S-EPMC2825114 | biostudies-literature

Muscarinic receptors: their roles in disorders of the central nervous system and potential as therapeutic targets.

Project description:Phylogenetically, acetylcholine is an ancient neurochemical. Therefore, it is not surprising that cholinergic neurons project extensively throughout the central nervous system, innervating a wide range of structures within the brain. In fact, acetylcholine is involved in processes that underpin some of our most basic central functions. Both muscarinic and nicotinic receptor families, which mediate cholinergic transmission, have been implicated in the pathophysiology of psychiatric and neurological disorders. The question that remains to be definitively answered is whether or not these receptors are viable targets for the development of future therapeutic agents.

| S-EPMC6493542 | biostudies-literature

Clinical proton MR spectroscopy in central nervous system disorders.

Project description:A large body of published work shows that proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of (1)H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of (1)H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which (1)H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units.

| S-EPMC4263653 | biostudies-literature

Melanoma central nervous system metastases: current approaches, challenges, and opportunities.

Project description:Melanoma central nervous system metastases are increasing, and the challenges presented by this patient population remain complex. In December 2015, the Melanoma Research Foundation and the Wistar Institute hosted the First Summit on Melanoma Central Nervous System (CNS) Metastases in Philadelphia, Pennsylvania. Here, we provide a review of the current status of the field of melanoma brain metastasis research; identify key challenges and opportunities for improving the outcomes in patients with melanoma brain metastases; and set a framework to optimize future research in this critical area.

| S-EPMC5398760 | biostudies-literature

The Therapeutic Prospects of Targeting IL-1R1 for the Modulation of Neuroinflammation in Central Nervous System Disorders.

Project description:The interleukin-1 receptor type 1 (IL-1R1) holds pivotal roles in the immune system, as it is positioned at the "epicenter" of the inflammatory signaling networks. Increased levels of the cytokine IL-1 are a recognized feature of the immune response in the central nervous system (CNS) during injury and disease, i.e., neuroinflammation. Despite IL-1/IL-1R1 signaling within the CNS having been the subject of several studies, the roles of IL-1R1 in the CNS cellular milieu still cause controversy. Without much doubt, however, the persistent activation of the IL-1/IL-1R1 signaling pathway is intimately linked with the pathogenesis of a plethora of CNS disease states, ranging from Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS), all the way to schizophrenia and prion diseases. Importantly, a growing body of evidence is showing that blocking IL-1R1 signaling via pharmacological or genetic means in different experimental models of said CNS diseases leads to reduced neuroinflammation and delayed disease progression. The aim of this paper is to review the recent progress in the study of the biological roles of IL-1R1, as well as to highlight key aspects that render IL-1R1 a promising target for the development of novel disease-modifying treatments for multiple CNS indications.

| S-EPMC8915186 | biostudies-literature

Therapeutic Approaches for Zika Virus Infection of the Nervous System.

Project description:Zika virus has spread rapidly in the Americas and has caused devastation of human populations affected in these regions. The virus causes teratogenic effects involving the nervous system, and in adults and children can cause a neuropathy similar to Guillain-Barré syndrome, an anterior myelitis, or, rarely, an encephalitis. While major efforts have been undertaken to control mosquito populations that spread the virus and to develop a vaccine, drug development that directly targets the virus in an infected individual to prevent or treat the neurological manifestations is necessary. Rational and targeted drug development is possible since the viral life cycle and the structure of the key viral proteins are now well understood. While several groups have identified therapeutic candidates, their approaches differ in the types of screening processes and viral assays used. Animal studies are available for only a few compounds. Here we provide an exhaustive review and compare each of the classes of drugs discovered, the methods used for drug discovery, and their potential use in humans for the prevention or treatment of neurological complications of Zika virus infection.

| S-EPMC5722777 | biostudies-literature

Sex and Gender Differences in Central Nervous System-Related Disorders.

Project description:There are important sex differences in the brain that seem to arise from biology as well as psychosocial influences. Sex differences in several aspects of human behavior and cognition have been reported. Gonadal sex steroids or genes found on sex chromosomes influence sex differences in neuroanatomy, neurochemistry and neuronal structure, and connectivity. There has been some resistance to accept that sex differences in the human brain exist and have biological relevance; however, a few years ago, it has been recommended by the USA National Institute of Mental Health to incorporate sex as a variable in experimental and clinical neurological and psychiatric studies. We here review the clinical literature on sex differences in pain and neurological and psychiatric diseases, with the aim to further stimulate interest in sexual dimorphisms in the brain and brain diseases, possibly encouraging more research in the field of the implications of sex differences for treating these conditions.

| S-EPMC4904110 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data